The primary goal of this research is to improve our understanding of the role of intercellular interactions in the developing central nervous system under normal and patoholical conditions. As a model system, I plan to examie the role of neuron-glia interactions in regulating the expression of the enzyme, sn-glycerol-3-phosphate dehydrogenase (GPDH), in BVergmann glia in the developing mouse cerebellum. This enzyme is differentially expressed during brain development, and in the cerebellum, GPDH is predominantly localized in two glial cell types, oligodendroglia and Bergmann glia. Preliminary evidence suggest that the expression of high levels of enzyme by Bergmann glia is dependent upon an early interactio between those cells and adjacent nerons, the Purkinje cells. This hypothesis will be tested with chimeric mice made by aggregating normalembryos with embryos bearing neuroligical mutations that alter the expression of GPDH. Besides affecting GPDH expression, the mutations to be used also result in Purkinje cell defects of varying severity. Analysis of chimeras will reveal whether normal enzyme expression by Bergmann glia requires the presence of normal Purkinje cells. An additional, but mino, componena of the research proposed involves analysis of new neurological mutations. Descriptive anatomial and embryological studies are planned to identify new mutations that might prove valuable in future studies of central nervous system development and function.